胶质母细胞瘤因子通过增加 MMP-9/CXCR4 水平促进人脑内皮细胞迁移。
Glioblastoma Factors Increase the Migration of Human Brain Endothelial Cells by Increasing MMP-9/CXCR4 Levels.
机构信息
Brain's Biomedicine Lab, Paulo Niemeyer State Brain Institute, Rio de Janeiro, Brazil.
Cellular Morphogenesis Lab, Biomedical Sciences Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
出版信息
Anticancer Res. 2020 May;40(5):2725-2737. doi: 10.21873/anticanres.14244.
BACKGROUND/AIM: Glioblastoma (GB) is the most aggressive type of tumor in the central nervous system and is characterized by resistance to therapy and abundant vasculature. Tumor vessels contribute to the growth of GB, and the tumor microenvironment is thought to influence tumor vessels. We evaluated the molecular communication between human GB cells and human brain microvascular endothelial cells (HBMEC) in vitro.
MATERIALS AND METHODS
We investigated whether GB-conditioned media (GB-CM) influenced HBMEC proliferation and migration, as well as the levels of MMP-9, CXCL12, CXCR4, CXCR7, VEGFs, VEGFR-2, and WNT5a in HBMEC.
RESULTS
Although HBMEC proliferation was not modified, increased HBMEC migration was detected after GB-CM treatment. Furthermore, treatment of HBMEC with GB-CM resulted in increased levels of MMP-9 and CXCR4. The levels of WNT5a, VEGFs and VEGFR-2 were not affected.
CONCLUSION
GB-secreted factors lead to increased endothelial cell migration and to increased levels of MMP-9 and CXCR4.
背景/目的：胶质母细胞瘤（GB）是中枢神经系统中最具侵袭性的肿瘤类型，其特征为对治疗的耐药性和丰富的血管生成。肿瘤血管有助于 GB 的生长，并且肿瘤微环境被认为会影响肿瘤血管。我们在体外评估了人胶质母细胞瘤细胞与人类脑微血管内皮细胞（HBMEC）之间的分子通讯。
材料和方法
我们研究了 GB 条件培养基（GB-CM）是否会影响 HBMEC 的增殖和迁移，以及 MMP-9、CXCL12、CXCR4、CXCR7、VEGFs、VEGFR-2 和 WNT5a 在 HBMEC 中的水平。
结果
尽管 HBMEC 的增殖没有改变，但在用 GB-CM 处理后检测到 HBMEC 迁移增加。此外，用 GB-CM 处理 HBMEC 会导致 MMP-9 和 CXCR4 水平升高。WNT5a、VEGFs 和 VEGFR-2 的水平不受影响。
结论
GB 分泌的因子导致内皮细胞迁移增加和 MMP-9 和 CXCR4 水平升高。
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